Congenital agenesis of the major salivary glands is a rare developmental anomaly. Awareness of this condition in children is limited, and differentiation from autoimmune or acquired causes of xerostomia, such as juvenile Sjögren’s disease, is essential for accurate diagnosis. A systematic search of PubMed, MEDLINE, Embase and Google Scholar was performed in accordance with PRISMA guidelines. Case reports describing congenital absence of all major salivary glands in patients aged under 18 were included. Data were extracted on demographics, presentation, pathology, imaging, presence of caries, lacrimal involvement and association with familial syndromes. Risk of bias was assessed using the JBI checklist for case reports. Twenty cases met the inclusion criteria. Mean age at presentation was 6.4 years (range 9 months–16 years). Xerostomia (80%) and dental caries (100%) were universal findings, and half of cases demonstrated lacrimal involvement. Pathological testing was variable, mainly used to exclude Sjögren’s disease. Tc-99m scintigraphy was the most common diagnostic modality. Only one patient had a confirmed FGFR2 mutation consistent with LADD syndrome. Congenital salivary gland agenesis is a rare but clinically significant cause of paediatric xerostomia and dental morbidity. Structured assessment including imaging, serology, and genetic testing is critical for early identification and management of cases to prevent complications.